BPA modulates the neutrophil response and cytokine environment in a model of tail fin regeneration

Abstract The ER-α and β ligand bisphenol A (BPA) is used in the production of polycarbonate plastic and epoxy resins. BPA presents a potential environmental challenge to both human and wildlife immunity due to its widespread use and its resulting presence in surface water and wastewater runoff. We observed that BPA exposure downregulates the expression of a neutrophil-recruiting chemokine in both mice (cxcl1) and zebrafish (cxcl8) and that BPA exposure decreases neutrophil recruitment to a tail injury in zebrafish. Neutrophils are essential for the removal of damaged tissue and invading microbes, thus facilitating tissue regeneration of the tail fin. To investigate BPA’s effects on larval zebrafish tail regeneration, we induced a tail injury at day 3 post fertilization (dpf) and found that fish exposed to 100 ng/ml BPA regenerate a smaller tail fin area at 3 dpi (p-value < 0.01). We hypothesized that neutrophil recruitment could be tied to regeneration by altering the expression of inflammation- and regeneration-related genes. 3 dpf embryos exposed to BPA show modulated levels of background wnt10a and il-10 expression compared to controls. BPA exposure reduces the 3 hour post-injury inflammatory response by decreasing both il-1 and il-6 expression. By modifying the cytokine environment both prior to and following infection and injury, BPA impacts both the inflammatory response and tissue regeneration. Multiple cytokine and chemokine genes are regulated by the transcription factor NF-kB and Wnt plays a key role in tissue regeneration; these two proteins also cross regulate one another. The impact of BPA on wnt10a and nfkb expression following tissue injury and LPS exposure will be discussed. Supported by Carleton College.